title: Effects of raltegravir on 2-long terminal repeat circle junctions in HIV type 1 viremic and aviremic patients.
abstract: Although 2-long terminal repeat (2-LTR) circles are only a fraction of the total viral DNA in infected cells, sequence analysis of 2-LTR circles reveals critical information regarding viral DNA synthesis and the nature of actively replicating virus. It was observed that a large proportion of the 2-LTR circular molecules in the peripheral blood mononuclear cell (PBMC) DNA of infected individuals are mutated at the circle junction. The integrase inhibitor raltegravir (RAL) blocks the strand transfer step of the integration of HIV-1; as a consequence of abortive integration a significant increase of episomal 2-LTR circles is observed. Moreover, it was demonstrated that in patients treated with highly active retroviral therapy (HAART) changes in 2-LTR concentration did not affect junction sequences and flanking regions of 2-LTR. Here we evaluated whether RAL therapy could have a differential impact on the 2-LTR circle junctional sequences in patients with different virological profiles at the time of starting RAL therapy. Sequence analysis indicates that RAL acts differently in the two populations.
authors.affiliation: 1 Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità , Rome, Italy .
authors.forename: Roberta
authors.initials: R
authors.lastname: Bona
authors.forename: Silvia
authors.initials: S
authors.lastname: Baroncelli
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Ettorre
authors.forename: Mauro
authors.initials: M
authors.lastname: Andreotti
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ceccarelli
authors.forename: Piero
authors.initials: P
authors.lastname: Filati
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Leone
authors.forename: Maria
authors.initials: M
authors.lastname: Blasi
authors.forename: Zuleika
authors.initials: Z
authors.lastname: Michelini
authors.forename: Clementina Maria
authors.initials: CM
authors.lastname: Galluzzo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mallano
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.forename: Andrea
authors.initials: A
authors.lastname: Cara
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D017422:Sequence Analysis, DNA
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium